Carlström M, Sällström J, Skøtt O, Larsson E, Wåhlin N, Persson A E G
Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden.
Acta Physiol (Oxf). 2007 Mar;189(3):293-301. doi: 10.1111/j.1748-1716.2006.01637.x.
Hypertension is a common disease in the industrialized world and approximately 5% of all cases are secondary to kidney malfunction. We have recently shown that hydronephrosis due to partial unilateral ureteral obstruction (PUUO) causes salt-sensitive hypertension in rats. The mechanisms are still unclear, but appear to be intrarenal and primarily located to the diseased kidney. In the present study, we have developed a model for PUUO to study if hydronephrotic mice develop salt-sensitive hypertension.
PUUO was created in 3-week-old mice (C57bl/6J). Blood pressure and heart rate were measured telemetrically in adult animals on normal and high salt diets. Metabolism cages were used to study the renal excretion of electrolytes and water. Plasma samples for renin analysis were collected and renal histological changes were evaluated.
All hydronephrotic animals developed salt-sensitive hypertension that correlated to the degree of hydronephrosis. In hydronephrotic animals, blood pressure increased from 114 +/- 1 mmHg on normal salt diet to 120 +/- 2 mmHg on high salt diet, compared with 103 +/- 1 to 104 +/- 1 in controls. Hydronephrotic animals showed increased diuresis and reduced ability to regulate electrolyte concentration. No differences in plasma renin concentration were found between the groups. The parenchymal weight and glomerular area of contralateral kidneys were significantly increased in the hydronephrotic animals. Histopathology of the hydronephrotic kidneys displayed areas with fibrosis, inflammation and glomerular changes.
This study provides a model for PUUO in mice and demonstrates the presence of salt-sensitive hypertension and an impaired renal concentrating ability in mice which has not been described before.
高血压在工业化国家是一种常见疾病，约5%的病例继发于肾脏功能障碍。我们最近发现，部分单侧输尿管梗阻（PUUO）所致肾积水会导致大鼠出现盐敏感性高血压。其机制尚不清楚，但似乎是肾内性的，主要位于患病肾脏。在本研究中，我们建立了一个PUUO模型，以研究肾积水小鼠是否会出现盐敏感性高血压。
在3周龄小鼠（C57bl/6J）中制造PUUO。对成年动物在正常和高盐饮食条件下进行遥测血压和心率。使用代谢笼研究电解质和水的肾脏排泄情况。收集血浆样本进行肾素分析，并评估肾脏组织学变化。
所有肾积水动物均出现盐敏感性高血压，且与肾积水程度相关。在肾积水动物中，正常盐饮食时血压从114±1 mmHg升高至高盐饮食时的120±2 mmHg，而对照组则从103±1 mmHg升高至104±1 mmHg。肾积水动物表现出利尿增加和调节电解质浓度的能力下降。两组之间血浆肾素浓度未发现差异。肾积水动物对侧肾脏的实质重量和肾小球面积显著增加。肾积水肾脏的组织病理学显示有纤维化、炎症和肾小球改变的区域。
本研究提供了一个小鼠PUUO模型，并证明了小鼠存在盐敏感性高血压以及肾脏浓缩能力受损，这在之前尚未被描述过。
